RESUMEN
Targeted selective treatment (TST) has been proposed as a sustainable method of gastrointestinal nematode control that reduces the number of anthelmintic treatments administered, thereby preserving a susceptible nematode population in refugia. In order to minimise the impact of withholding treatment on animal performance, animals that would benefit most should be selected for treatment. However, the most suitable criteria for selecting which animals to treat remain a subject of research. The impact of implementing a TST strategy based on lamb live weight was investigated, and whether heavy lambs were more resilient than light lambs if left untreated. The study was conducted using weaned lambs on 3 sheep farms, and over 2 years. On each farm lambs were weighed and divided into heavy, medium and light weight classes. Within the heavy (nâ¯=â¯225) and light (nâ¯=â¯218) weight classes lambs were randomly allocated to two treatments; anthelmintic treatment or no anthelmintic treatment. All lambs in the medium weight class were treated. Animal performance and parasitological parameters were assessed over a 28-day period. Anthelmintic treatment had a significant effect (Pâ¯<â¯0.01) on faecal egg count, average daily weight gain, body condition score and dag score; there was no treatment by weight class interaction. Anthelmintic treatment had no effect on plasma pepsinogen concentration or on blood leukocyte numbers. Withholding anthelmintic treatment from lambs therefore had a negative effect on worm egg count and animal performance with no evidence that heavy lambs were more resilient than light lambs when left untreated.
Asunto(s)
Antihelmínticos/uso terapéutico , Peso Corporal/efectos de los fármacos , Infecciones por Nematodos/veterinaria , Enfermedades de las Ovejas/tratamiento farmacológico , Animales , Antihelmínticos/administración & dosificación , Heces/parasitología , Femenino , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/parasitología , Leucocitos/efectos de los fármacos , Nematodos/efectos de los fármacos , Infecciones por Nematodos/tratamiento farmacológico , Infecciones por Nematodos/parasitología , Recuento de Huevos de Parásitos , Pepsinógeno A/sangre , Pepsinógeno A/efectos de los fármacos , Ovinos , Enfermedades de las Ovejas/parasitología , Destete , Aumento de PesoRESUMEN
OBJECTIVE: To assess the effect of a 2-week treatment with dexibuprofen, in comparison with ibuprofen and diclofenac, on pepsinogen plasma concentrations and gastrointestinal mucosa, as well as the correlation of these changes with gastrointestinal mucosal injury. METHODS: 60 patients with rheumatologic disease in chronic therapy with NSAID, were included. After a 7-day run-in period patients were randomly assigned to receive a 14-day treatment with dexibuprofen (Group A; Day 1 - 3 = 400 mg t.i.d; Day 4 - 14 = 400 mg b.i.d.), ibuprofen (Group B; Day 1 - 3 = 800 mg t.i.d; Day 4 -14 = 800 mg b.i.d.) or diclofenac (Group C; Day 1 - 3 = 50 mg t.i.d; Day 4 - 14 = 50 mg b.i.d.). Upper gastrointestinal endoscopy (Day 15), capsule-endoscopy (Day 16, 7 patients of each group) and determination of pepsinogen plasma concentrations were performed (basal and Day 15). A semiquantitative scale was designed for the assessment of the gastrointestinal mucosa. RESULTS: No differences in plasma pepsinogen were found between treatment groups or gastrointestinal injury grades or between basal and post-therapy determinations. Dexibuprofen showed gastroduodenal mucosal injury in fewer patients (42.1%) than was the case with ibuprofen (5%; p = 0.003) and diclofenac (30%; p = N.S.). Dexibuprofen administration was also associated with more patients having no intestinal mucosal damage (42.86% vs. 28.7% in the diclofenac group and 14.29% in the ibuprofen group; p = 0.0175). The rate of clinical adverse events was similar in Groups A, B and C (28%, 38% and 34%). CONCLUSIONS: Dexibuprofen showed a lower rate of gastroduodenal and intestinal mucosal injury. This effect was not mediated by modifications of plasma pepsinogen levels.
Asunto(s)
Inhibidores de la Ciclooxigenasa/efectos adversos , Diclofenaco/efectos adversos , Ibuprofeno/efectos adversos , Indoprofeno/efectos adversos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Pepsinógeno A/sangre , Administración Oral , Adulto , Inhibidores de la Ciclooxigenasa/farmacología , Diclofenaco/farmacología , Endoscopía Gastrointestinal , Femenino , Humanos , Ibuprofeno/farmacología , Indoprofeno/farmacología , Masculino , Persona de Mediana Edad , Pepsinógeno A/efectos de los fármacos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/patologíaRESUMEN
We examined the roles of cholecystokinin (CCK)-2 receptors in the regulation of pepsinogen secretion in the CCK-1 receptor deficient Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Pepsinogen secretion was determined in fasted acute fistula OLETF and control Long-Evans Tokusima Otsuka (LETO) rats. Pepsinogen secretion in OLETF rats under basal conditions as well as in response to CCK-8 stimulation was significantly higher than that in LETO rats. CCK-1 receptor specific agonist ARL 15849 was unable to stimulate pepsinogen secretion in OLETF rats, whereas it elicited pepsinogen secretion in LETO rats to levels similar to those obtained with equimolar CCK-8 stimulation. CCK-2 receptor antagonist reduced basal pepsinogen secretion and completely abolished CCK-8-stimulated pepsinogen output in OLETF rats, whereas in LETO rats, it reduced basal pepsinogen secretion but augmented CCK-8-stimulated pepsinogen output. CCK-1 receptor antagonist loxiglumide also greatly decreased CCK-8-stimulated pepsinogen secretion in OLETF rat, which indicates that loxiglumide is not a specific CCK-1 receptor antagonist. Intravenous infusion of somatostatin antagonist significantly increased CCK-8-stimulated pepsinogen secretion in LETO rats, whereas it had no significant influence on CCK-8-stimulated pepsinogen secretion in OLETF rats. These results indicate that CCK-8 stimulates pepsinogen secretion via CCK-2 receptors in CCK-1 receptor deficient OLETF rats and that the higher CCK-8-stimulated as well as basal pepsinogen secretion in OLETF rats might result from an elimination of tonic inhibition by somatostatin that is released from D cells through mainly CCK-1 receptors.
Asunto(s)
Pepsinógeno A/efectos de los fármacos , Pepsinógeno A/metabolismo , Receptor de Colecistoquinina A/deficiencia , Receptores de Colecistoquinina/antagonistas & inhibidores , Sincalida/farmacología , Animales , Modelos Animales de Enfermedad , Gastrinas/efectos de los fármacos , Gastrinas/metabolismo , Masculino , Probabilidad , Ratas , Ratas Endogámicas OLETF , Ratas Long-Evans , Valores de Referencia , Factores de Riesgo , Sensibilidad y Especificidad , Somatostatina/efectos de los fármacos , Somatostatina/metabolismo , Especificidad de la Especie , Estadísticas no ParamétricasRESUMEN
Protease-activated receptor-2 (PAR-2) is abundantly expressed in gastric mucosal chief cells, facilitating pepsinogen secretion. In the present study, we investigated whether PAR-1, a thrombin receptor, could modulate pepsinogen secretion in rats. The PAR-1-activating peptide TFLLR-NH(2) as well as the PAR-2-activating peptide SLIGRL-NH(2), administered i.v. repeatedly at 1-h intervals, significantly increased gastric pepsinogen secretion over 2-4 h (after two to four doses). In contrast, the control peptide FTLLR-NH(2), given in the same manner, had no such effect. Thus, PAR-1, like PAR-2, might function to facilitate pepsinogen secretion, suggesting a novel role of the thrombin-PAR-1-pathway in the stomach.
Asunto(s)
Oligopéptidos/farmacología , Pepsinógeno A/efectos de los fármacos , Pepsinógeno A/metabolismo , Animales , Inyecciones Intravenosas , Masculino , Oligopéptidos/administración & dosificación , Ratas , Ratas WistarRESUMEN
BACKGROUND: Peptides of cholecystokinin family regulate various physiological actions by acting at level of central nervous system. AIMS: To: 1) investigate possible influence of central cholecystokinin pathways on gastric pepsinogen and acid secretions; 2) characterize pharmacological profile and location of cholecystokinin receptor subtypes involved in gastric effects of centrally applied cholecystokinin-8-sulphate (cholecystokinin-8S). METHODS: Urethane-anaesthetized rats were subjected to continuous perfusion of gastric lumen. Pepsin levels in perfusate were determined by enzymatic assay based on spectrophotometric measurement of products generated by peptic digestion of bovine haemoglobin. Acidity was measured by automatic potentiometric titration of hydrogen ions. RESULTS: Following intracerebroventricular injection, cholecystokinin-8S increased both pepsinogen and acid output. In addition, intravenous cholecystokinin-8S stimulated peptic and acid secretions more promptly and at lower doses than after central injection. Stimulant effects of centrally applied cholecystokinin-8S were not affected by intracerebroventricular injection of devazepide (cholecystokinin A receptor antagonist) or L-365,260 (cholecystokinin B receptor antagonist) or by bilateral vagotomy. However, intravenous devazepide partly antagonized pepsigogue action of intracerebroventricular cholecystokinin-8S without affecting its acid hypersecretory effect, whereas after intravenous injection of L-365,260 peptic hypersecretion evoked by intracerebroventricular cholecystokinin-8S was partially prevented and acid response was completely blocked. Similar effects were exerted by intravenous devazepide and L-365,260 against intravenous cholecystokinin-8S. A complete blockade of pepsigogue effects induced by intracerebroventricular or intravenous cholecystokinin-8S was obtained after combined intravenous treatment with devazepide plus L-365,260. Gastric hypersecretory effects of intravenous cholecystokinin-8S were not modified by bilateral vagotomy. CONCLUSIONS: Increase in pepsinogen output evoked by centrally applied cholecystokinin-8S does not depend on interaction with central nervous sites. Following central or parenteral injection of cholecystokinin-8S, increase in peptic secretion would result from activation of both peripheral cholecystokinin A and B receptors presumably located at the level of gastric mucosa.
Asunto(s)
Colecistoquinina/farmacología , Ácido Gástrico/metabolismo , Pepsinógeno A/efectos de los fármacos , Receptores de Colecistoquinina/efectos de los fármacos , Análisis de Varianza , Animales , Benzodiazepinonas/farmacología , Colecistoquinina/administración & dosificación , Devazepida/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Antagonistas de Hormonas/farmacología , Inyecciones Intraventriculares , Masculino , Pepsinógeno A/metabolismo , Compuestos de Fenilurea/farmacología , Ratas , Ratas Wistar , Receptor de Colecistoquinina A , Receptor de Colecistoquinina B , Receptores de Colecistoquinina/antagonistas & inhibidores , Receptores de Colecistoquinina/fisiología , Estimulación Química , Factores de TiempoRESUMEN
OBJECTIVE: To determine which demographic factors may influence serum gastrin and pepsinogen I (PGI) levels in duodenal ulcer patients undergoing omeprazole treatment. METHODS: We conducted an outpatient-based prospective study in the Veterans General Hospital, Taipei, to investigate the pharmacological effects on patients with duodenal ulcers receiving omeprazole treatment for 4 weeks. Sixty-eight patients (61 males/7 females, aged 25 73 years) with endoscopically confirmed duodenal ulcer were included. Gastrin and pepsinogen I levels were measured before and after treatment. Demographic factors including age, sex, smoking, ulcer healing and antral Helicobacter pylori colonization/clearance were analyzed, in order to measure their probable influences on serum gastrin and pepsinogen I levels. RESULTS: Ulcer healing was seen in 92.6% of patients while 48 (70.6%) antral clearances were seen in 66 H. pylori colonized patients at the end of trial. Omeprazole monotherapy led to a marked elevation of serum gastrin (85.8 pg x ml(-1), SD 32.0 pg x ml(-1) vs 133.9 pg x ml(-1), SD 71.6 pg x ml(-1), P < 0.01), and pepsinogen I (111.0 ng x ml(-1), SD 36.7 ng x ml(-1) vs 253.6 ng x ml(-1) , SD 64.8 ng x ml(-1), P < 0.01) levels when measured on day 29. Only patients showing antral H. pylori clearance exhibited an influence on the magnitude of pepsinogen I elevation following omeprazole monotherapy (143.9%, SD 67.3% vs 78.6%, SD 51.2%, P < 0.01). Moreover, the sensitivity and specificity of serum pepsinogen I variations were plotted on a receiving operating characteristic (ROC) curve. The 140% increased pepsinogen I level yielded a maximum accuracy of 80% specificity or 50% sensitivity to predict antral H. pylori clearance. CONCLUSION: Antral H. pylori clearance is at least partially responsible for the omeprzaole-induced hyperpepsinogenemia I. The magnitude of hyperpepsinogenemia I probably provides a non-invasive alternative for predicting H. pylori clearance.
Asunto(s)
Úlcera Duodenal/sangre , Úlcera Duodenal/microbiología , Gastrinas/sangre , Helicobacter pylori/efectos de los fármacos , Omeprazol/uso terapéutico , Pepsinógeno A/sangre , Antro Pilórico/microbiología , Adulto , Factores de Edad , Anciano , Úlcera Duodenal/tratamiento farmacológico , Femenino , Gastrinas/efectos de los fármacos , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Pepsinógeno A/efectos de los fármacos , Factores Sexuales , Fumar/metabolismoRESUMEN
The model of permeable gastric glands obtained by its incubation with digiton (15 mg/ml) had investigated. It was shown, that stimulated influence of Ca2+ ions on pepsinogen extrusion completely or partly reproduced by cations of transient metals. Stimulated effects of cations of metals (5 x 10(-4) M) decrease in such order: Ca2+ > Cd2+ > Mn2+ > Co2+ > La3+. Nevertheless, Co2+ and La3+ in the same concentrations inhibit Ca2+ stimulated extrusion of pepsinogen by permeable isolated glands. Stimulated effect of Cd2+ and La3+ on pepsinogen extrusion in native glands was not reproducible. Besides these cations inhibit carbacholine-stimulated extrusion in native glands. It's concluded, that influence of metal cations on secretory function of gastric glands to a great extent is determined by their property to penetrate into secretory cells and cooperate with their plasma membranes.